ArticleNature structural & molecular biology2021
Mechanistic insight into substrate processing and allosteric inhibition of human p97.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 91 citations in OpenAlex.
- A selective NVL inhibitor suppresses tumor growth by targeting ribosome biogenesis.Nature chemical biology · 2026Article
- ATP-independent unfolding of ubiquitin by Ufd1 initiates Cdc48/p97-mediated substrate processing.Nature structural & molecular biology · 2026Article
- Organelle contact reorganization drives calcium-dependent autophagy under proteostatic stress.Autophagy · 2026Article
- FAF1 and FAF2 enhance unfolding by p97-UFD1-NPL4 complex enabling rational design of p97 activators.The EMBO journal · 2026Article
- FAF1 cofactor enhances UFD1/NPL4-p97 unfolding efficiency across ubiquitin chain lengths independent of SUMO2.bioRxiv : the preprint server for biology · 2026Article
- Proteomic Analysis Reveals That P97 Inhibitors Induce Ferroptosis in Gastric Cancer AGS Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The vacuolar tauopathy-associated mutation D395G confers redox sensitivity to p97/VCP.bioRxiv : the preprint server for biology · 2026Article
- Direct observation of ATP-driven ubiquitin chain handling by Cdc48.Nature communications · 2026Article
- The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation.Scientific reports · 2026Article
- The accessory adapters FAF1, FAF2, and UBXN7 accelerate proteasomal degradation by increasing prior p97-mediated substrate unfolding.Science advances · 2026Article
- Cryo-EM structural analyses reveal plant-specific adaptations of the CDC48 unfoldase.Plant communications · 2026Article
- Induced ubiquitination bypasses canonical ERAD to drive ER protein degradation.bioRxiv : the preprint server for biology · 2025Article
- The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation.bioRxiv : the preprint server for biology · 2025Article
- Advances in the chemical synthesis of human proteoforms.Science China. Life sciences · 2025Review
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Mechanism of nascent chain removal by the ribosome-associated quality control complex.Nature communications · 2025Article
- Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.The Journal of cell biology · 2025Article
- PEX1The Journal of biological chemistry · 2025Article
- 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.Neurobiology of disease · 2025Review
- Targeting EGFR-binding protein SLC7A11 enhancing antitumor immunity of T cells via inducing MHC-I antigen presentation in nasopharyngeal carcinoma.Cell death & disease · 2025Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with resolutions ranging from 2.9 to 3.8 Å that captured 'power-stroke'-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the intersubunit signaling (ISS) motifs, which tighten the binding of nucleotides and neighboring subunits and contribute to the spiral staircase conformation of the D1 and D2 rings. In addition, we determined the cryo-EM structure of human p97 in complex with NMS-873, a potent p97 inhibitor, at a resolution of 2.4 Å. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change and thus blocking substrate translocation allosterically.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.